For people with HIV-associated cryptococcal meningitis, how do different two-week induction therapies compare?

CIAPPONI, AGUSTÍN

Cochrane Clinical Answers

Cochrane Clinical Answers

Año: 2019

Moderate‐certainty evidence showed mortality for people with HIV‐associated cryptococcal meningitis is probably reduced with AmBd+5FC compared with AmBd alone. For other comparisons, results were too imprecise to draw firm conclusions. Fungal clearance was improved with AmBd+5FC. 5FC+FLU may be less commonly associated with anemia, hypokalemia and renal dysfunction than other regimens. However, many regimens were assessed in few people, primarily from high‐income countries, making it difficult to draw firm and generalizable conclusions.Reviewers made 12 comparisons of different two‐week induction therapies for people with HIV‐associated cryptococcal meningitis, which included flucytosine (5FC), fluconazole (FLU), amphotericin B deoxycholate (AmBd), interferon‐gamma (IFNg), and liposomal AmBd (L‐AmBd), alone or in combination.Moderate‐certainty evidence shows fewer people dying with AmBd+5FC than with AmBd alone (on average, 294 vs 444 per 1000 people). For the other comparisons, results were too imprecise to support conclusions. Fungal clearance was better with AmBd+5FC than with AmBd alone, 5FC+FLU or AmBd+FLU; and with AmBd+FLU than with 5FC+FLU or AmBd+FLU+steroids. Researchers reported little to no difference between AmBd+FLU and AmBd alone. In terms of adverse events, reviewers assessed anemia, renal dysfunction, neutropenia, hypokalemia, and alanine aminotransferase (ALT) abnormality (ALT abnormality was not assessed for all comparisons). Researchers reported that fewer people developed:? anemia with 5FC+FLU than with AmBd+5FC or AmBd+FLU; and with AmBd+FLU or AmBd+5FC than with AmBd alone;? hypokalemia with 5FC+FLU than with AmBd+5FC or AmBd+FLU; and with AmBd+FLU+steroids than with AmBd+FLU;? neutropenia with AmBd than with AmBd+FLU or AmBd+5FC; and with AmBd+FLU+steroids than with AmBd+FLU;? renal dysfunction with 5FC+FLU than with AmBd+FLU; and with AmBd+FLU than with AmBd+FLU+ steroids; or?ALT abnormality with AmBd+FLU than with AmBd+FLU+steroids.Comparisons of: FLU vs FLU+5FC; L‐AmBd vs AmBd; AmBd+5FC+FLU vs AmBd+5FC, AmBd+FLU or AmBd; and AmBd+5FC+IFNg vs AmBd+5FC were evaluated in too few participants to be clinically useful (26 to 98 participants).